Shared genetic architecture between metabolic traits and Alzheimer's disease: a large-scale genome-wide cross-trait analysis

Human Genetics
Zhaozhong ZhuLiming Liang

Abstract

A growing number of studies clearly demonstrate a substantial link between metabolic dysfunction and the risk of Alzheimer's disease (AD), especially glucose-related dysfunction; one hypothesis for this comorbidity is the presence of a common genetic etiology. We conducted a large-scale cross-trait GWAS to investigate the genetic overlap between AD and ten metabolic traits. Among all the metabolic traits, fasting glucose, fasting insulin and HDL were found to be genetically associated with AD. Local genetic covariance analysis found that 19q13 region had strong local genetic correlation between AD and T2D (P = 6.78 × 10- 22), LDL (P = 1.74 × 10- 253) and HDL (P = 7.94 × 10- 18). Cross-trait meta-analysis identified 4 loci that were associated with AD and fasting glucose, 3 loci that were associated with AD and fasting insulin, and 20 loci that were associated with AD and HDL (Pmeta < 1.6 × 10- 8, single trait P < 0.05). Functional analysis revealed that the shared genes are enriched in amyloid metabolic process, lipoprotein remodeling and other related biological pathways; also in pancreas, liver, blood and other tissues. Our work identifies common genetic architectures shared between AD and fasting glucose, fasting insulin and...Continue Reading

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Citations

Oct 18, 2019·The European Respiratory Journal·Zhaozhong ZhuLiming Liang
Sep 5, 2020·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Erin R Hascup, Kevin N Hascup
Sep 18, 2020·Science Translational Medicine·Sonia García-CalzónCharlotte Ling
Feb 9, 2021·Journal of Alzheimer's Disease : JAD·Jing ZhouPaul K Crane
Feb 11, 2021·International Journal of Molecular Sciences·Leonor Jacobo-AlbaveraTeresa Villarreal-Molina
Apr 6, 2021·Frontiers in Aging Neuroscience·David VogrincVita Dolžan

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Methods Mentioned

BETA
footprinting

Software Mentioned

METAL
ImpG
HESS
LiftOver
FGFINSmeta
FUSION
CPASSOC
PLINK
SHet
R package Cross - Phenotype Association ( CPASSOC )

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